Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

Immunometabolism

Itaconate boosts type I IFN response by disrupting cytoprotection

Nature Metabolism volume 7, pages 1106–1108 (2025)Cite this article

Subjects

A new study reveals a surprising mechanism by which itaconate inhibits the active site of a peroxiredoxin enzyme to amplify redox signalling and the type I interferon response in macrophages.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Inhibition of peroxiredoxin 5 increases the availability of hydrogen peroxide, mitochondrial permeability and expression of type I IFN.

References

  1. Martínez-Reyes, I. & Chandel, N. S. Nat. Commun. 11, 102 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Peace, C. G. & O’Neill, L. A. J. Clin. Invest. 132, e148548 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Luan, H. H. & Medzhitov, R. Cell Metab. 24, 379–387 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Mills, E. L. et al. Cell 167, 457–470.e13 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ramalho, T. et al. Cell Metab. 36, 484–497.e6 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. O’Carroll, S. M. et al. Nat. Metab. 6, 2060–2069 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Paulenda, T. et al. Nat. Metab. https://doi.org/10.1038/s42255-025-01275-0 (2025).

    Article  PubMed  Google Scholar 

  8. Lampropoulou, V. et al. Cell Metab. 24, 158–166 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Fuertes, M. B., Woo, S. R., Burnett, B., Fu, Y. X. & Gajewski, T. F. Trends Immunol. 34, 67–73 (2013).

    Article  CAS  PubMed  Google Scholar 

  10. Rhee, S. G. & Woo, H. A. Antioxid. Redox Signal. 15, 781–794 (2011).

    Article  CAS  PubMed  Google Scholar 

  11. Hanschmann, E. M., Godoy, J. R., Berndt, C., Hudemann, C. & Lillig, C. H. Antioxid. Redox Signal. 19, 1539–1605 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Patel, M. N. et al. Trends Mol. Med. 23, 165–180 (2017).

    Article  CAS  PubMed  Google Scholar 

  13. Bambouskova, M. et al. Cell Rep. 34, 108756 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Billingham, L. K. et al. Nat. Immunol. 23, 692–704 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Guarda, G. et al. Immunity 34, 213–223 (2011).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA

    Theresa Ramalho

  2. Department of Medicine, Division of Infectious Disease and Immunology, University of Massachusetts Chan Medical School, Worcester, MA, USA

    Ricardo Tostes Gazzinelli

  3. Centro de Tecnologia de Vacinas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

    Ricardo Tostes Gazzinelli

  4. Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Brazil

    Ricardo Tostes Gazzinelli

Authors
  1. Theresa Ramalho
    View author publications

    Search author on:PubMed Google Scholar

  2. Ricardo Tostes Gazzinelli
    View author publications

    Search author on:PubMed Google Scholar

Corresponding authors

Correspondence to Theresa Ramalho or Ricardo Tostes Gazzinelli.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ramalho, T., Gazzinelli, R.T. Itaconate boosts type I IFN response by disrupting cytoprotection. Nat Metab 7, 1106–1108 (2025). https://doi.org/10.1038/s42255-025-01274-1

Download citation

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s42255-025-01274-1

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing